The pancreas is an organ having exocrine functions of secreting and sending pancreatic juice containing digestive enzymes into the alimentary canal and endocrine functions of secreting hormones such as insulin and glucagon into the blood. Endocrine depend on cell clusters scattered within the pancreas, referred to as islets of Langerhans. At least 95% of the pancreas is responsible for exocrine functions. The pancreatic juice secreted from exocrine pancreatic cells passes through the pancreatic duct and then travels to the duodenum via the duodenal papillary.
When inflammation continuously occurs in exocrine gland cells for a long period of time, the cells are gradually disrupted and then replaced by fibrous tissue, which induces chronic pancreatitis. Chronic pancreatitis is induced by pancreatic duct obstruction due to heavy alcohol consumption, gallstones, or the like, but may also be induced by unknown causes. Conservative therapy (e.g., the administration of a digestive enzyme drug) has been conducted for chronic pancreatitis. However, no basic therapeutic method has been established.
In recent years, pluripotent cells such as induced pluripotent stem cells (iPS cells), which are obtained by introducing an undifferentiated cell-specific gene into embryonic stem cells (ES cells) or somatic cells, have been reported. The elucidation of the cause of the aforementioned disease and the development of a therapeutic agent using tissue somatic cells obtained from such cells has been desired.
Pancreatic precursor cells capable of differentiating into endocrine cells and exocrine cells express PDX1. Hence, with the use of the PDX1 as a gene marker, a method for induction of pancreatic precursor cells from pluripotent stem cells has been developed (Chen S, et al., Nat Chem Biol. 2009, 5, 258-265). Many studies have been conducted concerning methods for inducing insulin-producing cells from the thus obtained pancreatic precursor cells. However, there have been few findings on differentiation-induction methods that are specialized for exocrine pancreatic cells.